期刊
HYPERTENSION
卷 73, 期 5, 页码 E14-E24出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.118.12319
关键词
angiotensin II; blood pressure; inflammation; macrophages; mice
资金
- Natural Science Foundation of Shanghai Science and Technology Committee [16ZR1429300]
- open subject of Chinese Academy of Sciences [201501]
Regulatory T cells (T-reg cells) play important roles in hypertension and organ damages. MicroRNA-31 (miR-31) is a critical regulator for T-reg cell generation. However, the role of miR-31 in hypertension has not been elucidated. We aim to study the functionality of miR-31 and the detailed mechanism in Ang II (Angiotensin II)-induced hypertensive mouse model. We found: In vitro, miR-31 expression was higher in T helper 17 cells and lower in T-reg cells than that of naive T cells. The genetic deficiency of miR-31 promoted T-reg cell differentiation, whereas no impact on T helper 17 cells differentiation. Ang II-induced hypertension resulted in increased expression of miR-31 in the aorta, splenic CD4(+) T cells, and kidney leukocytes. MiR-31 deficiency strikingly decreased systolic blood pressure and diastolic blood pressure and attenuated renal and vascular damage. MiR-31 deletion altered the accumulation of T-reg cells and macrophages and expression of inflammatory cytokines in kidneys in Ang II-induced hypertensive mice. Ang II treatment reduced the levels of anti-inflammatory cytokines and increased proinflammatory cytokines in plasma that were blunted by the miR-31 deletion. Ppp6C (protein phosphatase 6c; a direct target of miR-31) specific deletion in T-reg cells led to marked impairment of T-reg cell induction, increased Ang II-induced blood pressure elevation, and organ damage in mice. In conclusion, we provided novel evidence of miR-31 as an emerging key posttranscriptional regulator of hypertension-associated immunosuppression through targeting ppp6C which is a critical regulator in the differentiation of T-reg cells. This study offers new perspectives on miRNA-based therapeutic approaches.
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